Adsorptive blood purification therapy consisting in positively removing, from the blood of patients, pathogenic substances occurring therein has been attempted energetically and has been found effective against a number of intractable diseases. Two techniques are available for adsorptive blood purification therapy, namely plasma perfusion and direct hemoperfusion. The plasma perfusion technique is a two-step system comprising plasma separation means and blood purification means and thus requires an apparatus to serve exclusively for safe operation, hence the treatment cost goes up and a complicated operation is required. On the other hand, the direct hemoperfusion technique is a one-step system in which the blood is directly perfused through an adsorber; therefore, the operation is simple and easy, and the amount of the extracorporeally circulated blood is small, so that the load on patients can be reduced. However, one of the problems encountered by the adsorber for direct hemoperfusion is the occurrence of water-insoluble microparticles in the adsorber.
Water-insoluble microparticles are mainly of adsorbent origin and, theoretically, can flow out from the adsorbent and enter the human body on the occasion of treatment by direct hemoperfusion. In case where water-insoluble microparticles enter the body in large amounts, such serious safety problems as vascular occlusion and accumulation in organs are anticipated.
Typical examples of the direct hemoperfusion adsorber which are currently available on the market are the following (cf. Non-Patent Document 1).
One is KANEKA CORPORATION's adsorber for removing β2 microglobulin (molecular weight: about 12,000). The adsorbent (cf. Non-Patent Document 2) used in this adsorber has a particle diameter of about 500 μm with a uniform particle diameter distribution. As for the intended use, the adsorber is applied in the treatment of amyloidosis accompanied by arthralgia and utilized on the occasion of hemodialysis. Since the adsorbent is uniform in particle diameter distribution, it is easy to remove water-insoluble microparticles without the loss of the adsorbent by using a device for removing water-insoluble microparticles (cf. Patent Document 1), for instance. Thus, the use of such an adsorbent uniform in particle diameter distribution is a measure against water-insoluble microparticles. However, a special granulation apparatus (cf. Patent Document 3) is required for the production of an adsorbent uniform in particle diameter distribution (cf. Patent Document 2). The actual situation is that any general-purpose water-insoluble carrier uniform in particle diameter distribution and capable of being applied as an adsorbent carrier is not commercially available.
Another one is KURARAY MEDICAL, INC.'s kidney-assisting adsorptive blood purifier. The adsorbent (cf. Non-Patent Document 2) used in this adsorber is 400 to 900 μm in particle diameter and is used as a kidney assistant for removing uremia-causing substances (molecular weight: about 100 to 2,000). For use in direct hemoperfusion adsorbent, active carbon is surface-coated with poly(hydroxyethyl methacrylate) so that water-insoluble microparticles may not be released. That is, the adsorbent has a coating as a measure against water-insoluble microparticles. However, it is necessary to provide the adsorbent with a coating, so that the production process becomes complicated.
As explained above, these adsorbers are produced, for use in direct hemoperfusion, by particular processes considering the water-insoluble microparticle-related safety problem. Due to the necessity of those particular processes, the production costs of products inevitably increase. Accordingly, a direct hemoperfusion adsorber that can be obtained in a simple and easy manner using a general-purpose water-insoluble carrier, for instance, without requiring any special granulation apparatus or coating apparatus is desired.
A patent specification has so far been laid open concerning the removal of water-insoluble microparticles from an adsorbent for medical use (cf. Patent Document 1). However, the technology disclosed therein is characterized by using a plurality of circulation and microparticle removal lines. The specification neither describes the particle diameter distribution of the adsorbent from which water-insoluble microparticles are to be removed nor specifies the ratio of the mesh opening size for removing water-insoluble microparticles to the mesh opening size of the adsorber.    Patent Document 1: Japanese Kokai Publication Hei-04-145941    Patent Document 2: Japanese Kokai Publication Hei-01-275601    Patent Document 3: Japanese Kokai Publication Sho-62-191033    Non-Patent Document 1: Japan Medical Devices Manufacturers Association: Specified Health Insurance Medical Materials Guidebook, pp. 175-, 2003    Non-Patent Document 2: Zinko Zoki (Japanese Journal of Artificial Organs), Vol. 23, No. 2, pp. 439-, 1994    Non-Patent Document 3: Kagaku Kogaku (Chemical Engineering of Japan), Vol. 50, No. 10, pp. 685-, 1986)